Tamoxifen perturbs lipid bilayer order and permeability: comparison of DSC, fluorescence anisotropy, Laurdan generalized polarization and carboxyfluorescein leakage studies
Tamoxifen perturbs lipid bilayer order and permeability: comparison of DSC, fluorescence anisotropy, Laurdan generalized polarization and carboxyfluorescein leakage studies
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DOI：
10.1016/s0301-4622(01)00139-9
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发表时间：
2001-04-10
影响因子：
3.8
通讯作者：
Diehl, H
中科院分区：
文献类型：
--
作者：
Engelke, M;Bojarski, P;Diehl, H
他莫昔芬对脂质双分子层结构的扰动可能与其与雌激素受体无关的多种抗癌机制有关。本研究利用差示扫描量热法（DSC）、1,6-二苯基-1,3,5-己三烯（DPH）和1-[4-[三甲基铵)苯基]-6-苯六烯-1,3,5-三烯（TMA-DPH）的荧光各向异性以及6-十二烷基-2-二甲氨基萘（Laurdan）广义极化，评价了他莫昔芬对模型膜结构特性的影响。对双棕榈酰磷脂酰胆碱（DPPC）制备的多片囊泡（MLV）进行了对比测量，结果表明他莫昔芬降低了相变温度（T-m），并使相变曲线变宽。在以蛋黄磷脂酰胆碱（EPC）为原料制备的大单层囊泡（LUV）中，他莫昔芬主要在外层区域增加脂质双层秩序。从膜渗透性测量中，我们得出结论，他莫昔芬诱导的捕获的羧基荧光素（CF）的释放是由于永久性的双分子层破坏和脂质双分子层中瞬时空洞的形成。(C) 2001 Elsevier Science b.v.，版权所有。
The perturbation of the lipid bilayer structure by tamoxifen may contribute to its multiple mechanisms of anticancer action not related to estrogen receptors. This study evaluates the effect of tamoxifen on structural characteristics of model membranes using differential scanning calorimetry (DSC), fluorescence anisotropy of 1,6-diphenyl-1,3,5-hexatriene (DPH) and 1-[4-[trimethylammonium)phenyl]-6-phenylhexa-1,3,5-triene (TMA-DPH), as well as 6-dodecanoyl-2-dimethylaminonaphthalene (Laurdan) generalized polarization. The comparative measurements in multilammelar vesicles (MLV) prepared from dipalmitoylphosphatidylcholine (DPPC) revealed that tamoxifen decreases the phase transition temperature (T-m) paralleled by a broadening of the phase transition profile. In large unilamellar Vesicles (LUV) prepared from egg yolk phosphatidylcholine (EPC), tamoxifen increased the lipid bilayer order predominantly in the outer bilayer region. From membrane permeability measurements, we conclude that the tamoxifen-induced release of entrapped carboxyfluorescein (CF) results from a permanent bilayer disruption and the formation of transient holes in the lipid bilayer. (C) 2001 Elsevier Science B.V.,All rights reserved.